Harrell Carl Randall, Volarevic Vladislav
Regenerative Processing Plant LLC, 13700 Reptron Blvd, Tampa, FL 33626, USA.
Center for Research on Harmful Effects of Biological and Chemical Hazards, Departments of Genetics, Microbiology and Immunology, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
Cells. 2024 Dec 6;13(23):2017. doi: 10.3390/cells13232017.
Dry eye disease (DED) is a common multifactorial disorder characterized by a deficiency in the quality and/or quantity of tear fluid. Tear hyperosmolarity, the dysfunction of ion channel proteins, and eye inflammation are primarily responsible for the development and progression of DED. Alterations in the structure and/or function of ion channel receptors (transient receptor potential ankyrin 1 (TRPA1), transient receptor potential melastatin 8 (TRPM8), transient receptor potential vanilloid 1 and 4 (TRPV1 and TRPV4)), and consequent hyperosmolarity of the tears represent the initial step in the development and progression of DED. Hyperosmolarity triggers the activation of ion channel-dependent signaling pathways in corneal epithelial cells and eye-infiltrated immune cells, leading to the activation of transcriptional factors that enhance the expression of genes regulating inflammatory cytokine production, resulting in a potent inflammatory response in the eyes of DED patients. A persistent and untreated detrimental immune response further modifies the structure and function of ion channel proteins, perpetuating tear hyperosmolarity and exacerbating DED symptoms. Accordingly, suppressing immune cell-driven eye inflammation and alleviating tear hyperosmolarity through the modulation of ion channels in DED patients holds promise for developing new therapeutic strategies. Here, we summarize current knowledge about the molecular mechanisms responsible for the inflammation-induced modification of ion channels leading to tear hyperosmolarity and immune cell dysfunction in DED patients. We also emphasize the therapeutic potential of the newly designed immunomodulatory and hypo-osmotic solution d-MAPPS™ Hypo-Osmotic Ophthalmic Solution, which can activate TRPV4 in corneal epithelial cells, stabilize the tear film, enhance natural cytokine communication, and suppress detrimental immune responses, an important novel approach for DED treatment.
干眼疾病（DED）是一种常见的多因素疾病，其特征在于泪液的质量和/或数量不足。泪液高渗、离子通道蛋白功能障碍和眼部炎症是干眼疾病发生和发展的主要原因。离子通道受体（瞬时受体电位锚蛋白1（TRPA1）、瞬时受体电位褪黑素8（TRPM8）、瞬时受体电位香草酸1和4（TRPV1和TRPV4））的结构和/或功能改变以及随之而来的泪液高渗是干眼疾病发生和发展的初始步骤。高渗触发角膜上皮细胞和眼部浸润免疫细胞中离子通道依赖性信号通路的激活，导致转录因子的激活，这些转录因子增强调节炎性细胞因子产生的基因的表达，从而在干眼患者的眼中引发强烈的炎症反应。持续且未治疗的有害免疫反应会进一步改变离子通道蛋白的结构和功能，使泪液高渗持续存在并加重干眼症状。因此，通过调节干眼患者的离子通道来抑制免疫细胞驱动的眼部炎症并减轻泪液高渗，有望开发新的治疗策略。在此，我们总结了目前关于导致干眼患者炎症诱导的离子通道修饰从而导致泪液高渗和免疫细胞功能障碍的分子机制的知识。我们还强调了新设计的免疫调节和低渗溶液d-MAPPS™低渗眼用溶液的治疗潜力，它可以激活角膜上皮细胞中的TRPV4，稳定泪膜，增强天然细胞因子通讯，并抑制有害免疫反应，这是一种重要的干眼治疗新方法。
